DPSCs May Be Useful in the Treatment of Neurological Disorders such as Alzheimer's Disease
Dental pulp stem cells (DPSCs) have the ability to differentiate into neurons for potential use in the treatment of neurological disorders involving a decline in cognitive abilities in humans.
Anim Cells Syst (Seoul). 2019 Jun 10;23(4):275-287. doi: 10.1080/19768354.2019.1626280. eCollection 2019.
Kang YH1,2, Shivakumar SB3, Son YB3, Bharti D3, Jang SJ3, Heo KS2, Park WU4, Byun JH1, Park BW1,2, Rho GJ3.
- Department of Dentistry, Gyeongsang National University School of Medicine and Institute of Health Science, Jinju, Republic of Korea.
- Department of Oral and Maxillofacial Surgery, Changwon Gyeongsang National University Hospital, Changwon, Republic of Korea.
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
- Department of Dental Technology, Jinju Health College, Jinju, Republic of Korea.
A decrease in the activity of choline acetyltransferase, the enzyme responsible for acetylcholine synthesis in the cholinergic neurons cause neurological disorders involving a decline in cognitive abilities, such as Alzheimer’s disease. Mesenchymal stem cells (MSCs) can be used as an efficient therapeutic agents due to their neuronal differentiation potential. Different source derived MSCs may have different differentiation potential under different inductions. Various in vitro protocols have been developed to differentiate MSCs into specific neurons but the comparative effect of different protocols utilizing same source derived MSCs, is not known. To address this issue, dental pulp derived MSCs (DPSCs) were differentiated into cholinergic neurons using three different protocols. In protocol I, DPSCs were pre-induced with serum-free ADMEM containing 1 mM of β-mercaptoethanol for 24 h and then incubated with 100 ng/ml nerve growth factor (NGF) for 6 days. Under protocol II, DPSCs were cultured in serum-free ADMEM containing 15 µg/ml of D609 (tricyclodecan-9-yl-xanthogenate) for 4 days. Under protocol III, the DPSCs were cultured in serum-free ADMEM containing 10 ng/ml of basic fibroblast growth factor (bFGF), 50 µM of forskolin, 250 ng/ml of sonic hedgehog (SHH), and 0.5 µM of retinoic acid (RA) for 7 days. The DPSCs were successfully trans-differentiated under all the protocols, exhibited neuron-like morphologies with upregulated cholinergic neuron-specific markers such as ChAT, HB9, ISL1, BETA-3, and MAP2 both at mRNA and protein levels in comparison to untreated cells. However, protocol III-induced cells showed the highest expression of the cholinergic markers and secreted the highest level of acetylcholine.
PMID: 31489249 PMCID: PMC6711138 DOI: 10.1080/19768354.2019.1626280